What if the insides of bacterial cells were more like glass than water? New research suggests that bacterial cytoplasm behaves like liquid glass – a result that could better explain cellular reaction kinetics. Read more...

When contemplating the inside of a bacterial cell, most researchers assume it
behaves like a fluid-filled sac. Not a water balloon exactly—the cytoplasm
is too chock-full of macromolecules to behave like water—but something more
viscous, like a balloon filled with glycerol.

The implication here is that the cell is effectively homogeneous with enzymes
and metabolites freely diffusing and that their concentrations are the key
to reaction kinetics. At least this is the way biochemists traditionally
have modeled the cell.

As it turns out, that model is overly simplistic. In a new study, researchers
demonstrated that bacterial cytoplasm actually is more akin to glass—or,
rather, a glass-forming liquid very near to the so-called glass transition.
In this environment, relatively small molecules and proteins appear to move
by diffusion. Particles larger than about 30 nm, the size of a ribosome,
move far more slowly, a result of the fluid’s glass-like properties. Even
more remarkably, metabolic activity appears to “fluidize” the cytoplasm,
making it possible for larger particles to move more freely in a
metabolically active cell than in a dormant one.

That observation, which reconciles previous conflicting data on cytoplasmic
motion, has wide-ranging implications for processes ranging from the
movement of chromosomes and plasmids during partitioning, to the assembly of
virus particles, said Christine Jacobs-Wagner, Professor of Molecular,
Cellular and Developmental Biology at Yale University and an Investigator of
the Howard Hughes Medical Institute, who led the study which appeared in the
January 16 issue of the journal Cell (1).

“If you affect cellular dynamics, you affect the physiology and the behavior
of the cell, because all biological processes are affected,” Jacobs-Wagner
said. “Biological macromolecules and complexes have to be able to move to
function; they have to be able to find one another and interact.”

According to Jacobs-Wagner, the link between cytoplasmic fluid dynamics and
metabolic activity was discovered by accident. A graduate student was using
motion tracking to study a fluorescently tagged filament protein in the
bacterium, Caulobacter crescentus. At first, the particles moved
freely throughout the cell. But at some point, the student noticed the
filament motion abruptly came to a halt. At the same time, the cells also
stopped growing.

That observation, Jacobs-Wagner said, “blew our mind.” Suspecting that
metabolic activity somehow was the key, the team applied treatments that
would force the cells into dormancy, such as removing carbon sources or
sapping ATP reserves. Those treatments caused the particles essentially to
freeze in place, The team also observed similar behavior in a different
bacterial species, Escherichia coli.

According to Jacobs-Wagner, viscosity isn’t sufficient to explain the behavior
and dynamics of different particles. “If it were [a viscosity effect], small
and big particles would see the environment the same way,” she said. “But
larger particles perceive the environment differently than small particles,
even though they are in the same environment.”

Instead, she said, the cytoplasm behaves like colloidal glass, an analogy that
makes sense in light of how crowded the cytoplasm really is. (A colloidal
glass is one in which a liquid containing a high concentration of particles
begins to flow ever more slowly until it eventually stops moving
altogether.)

And, similar to glass-like liquids near the glass transition, the cytoplasm
appears to be highly sensitive to perturbation. In colloidal glasses,
Jacobs-Wagner said, physical agitation can fluidize the system. It is
possible, she explained, that biochemical activity does the same thing in
the cell by essentially shaking up jammed components, causing them to
rearrange and move large distances.

Hugues Berry, a Senior Researcher at the French National Institute for
Research in Computer Science & Control (INRIA) and the University of
Lyon, who studies intracellular dynamics using mathematical modeling, said
the findings potentially explain bacterial dormancy.

“Let’s say that your metabolism is high and you have many, many reactions
occurring, and then suddenly you cut off the food source and you have to
stop metabolic activity,” Berry said. “You have to cool down your
metabolism. How do you do that? One way to cool down is to hinder molecular
encounters.”

Alternatively, he suggested, this glass-like behavior could provide a
mechanism for producing distinct molecular environments in cells that have
no internal membranes.

Whatever the reason, it’s now clear that the bacterial cytoplasm is more
complicated than a water balloon. “Our study is raising a lot more questions
than it is answering,” Jacobs-Wagner said. “But it makes us think the
cytoplasm has a different physical nature than we often assume.”